Submissions for variant NM_001376.5(DYNC1H1):c.5985C>T (p.Ala1995=)

gnomAD frequency: 0.00059  dbSNP: rs140841480

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000194990	SCV000247214	benign	not specified	2017-05-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000470101	SCV000512899	benign	not provided	2019-04-18	criteria provided, single submitter	clinical testing
Invitae	RCV001083329	SCV000559813	benign	Charcot-Marie-Tooth disease axonal type 2O	2024-01-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002317678	SCV000851686	likely benign	Inborn genetic diseases	2017-05-22	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000768205	SCV000898656	uncertain significance	Autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures; Charcot-Marie-Tooth disease axonal type 2O; Intellectual disability, autosomal dominant 13	2021-03-30	criteria provided, single submitter	clinical testing	DYNC1H1 NM_001376 exon 30 p.Ala1995Ala (c.5985C>T): This variant has not been reported in the literature but is present in 103/126648 European alleles, including 1 homozygote in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs140841480). This variant is present in ClinVar (Variation ID:210873). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant is a silent variant and does not change the amino acid, reducing the probability that this variant is disease causing. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
CeGaT Center for Human Genetics Tuebingen	RCV000470101	SCV001149332	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	DYNC1H1: BP4, BP7
Illumina Laboratory Services, Illumina	RCV001083329	SCV001267953	likely benign	Charcot-Marie-Tooth disease axonal type 2O	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001110505	SCV001267954	likely benign	Autosomal dominant cerebellar ataxia	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001172871	SCV001335944	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003907682	SCV004722017	likely benign	DYNC1H1-related condition	2019-12-20	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).